P642: IMPACT OF TYPE 2 DIABETES ON SURVIVAL AND TREATMENT IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: E. Curovic Rotbain, K. Rostgaard, M. A. Andersen, N. Vainer, C. Da Cunha-Bang, H. Hjalgrim, H. Frederiksen, S. Slager, C. Utoft Niemann
Journal: HemaSphere (2022)

Background: Because of a generally advanced age at diagnosis of chronic lymphocytic leukemia (CLL), this group of patients is often burdened by comorbid conditions. Comorbid conditions are associated with increased mortality in CLL, due to causes both related and unrelated to CLL. Diabetes is one of the most common comorbid conditions with a prevalence of 8-21% at time of CLL-diagnosis, and the prevalence of diabetes is projected to double in the general population within the next two decades. While many comorbid conditions may have limited potential for improvement of management, treatment for type 2 diabetes (T2D) is rapidly evolving with new treatment combinations displaying survival benefits. Aims: To assess the impact of T2D on time to treatment and mortality for patients with CLL from time of diagnosis and from time of first-line treatment. Methods: In Denmark, all citizens have access to free health care services. Contacts with the health care system are registered by the unique personal identification number, enabling linkage of data on person level across national registers. We followed all patients registered with newly diagnosed CLL in the Danish CLL Register or the Danish Cancer Register in the period 2002-2018 from 1 month after CLL-diagnosis until death or end of follow-up. Data on causes of death were obtained through the Danish National Register of Causes of Death. T2D was defined as having an International Classification of Diseases-10 diagnosis of T2D (E11) in the Danish National Patient Register or ≥1 prescription for non-insulin anti-diabetic drugs (ATC code A10B) in the Danish Prescription Register. Fine-Gray and Cox proportional hazards regressions were fitted, and corresponding Kaplan-Meier curves computed. Results: In total, 7 446 patients with CLL were identified, of whom 802 (11%) had T2D at CLL diagnosis. T2D was associated with longer time to first treatment (hazard ratio (HR) 0.81, 95% confidence interval (CI) [0.67-0.99]) and higher mortality (HR 1.58, 95% CI [1.42-1.76]) from time of CLL diagnosis. Patients with T2D had an increased mortality due to causes both related (HR 1.15, 95% CI [0.99-1.34]) and unrelated (HR 2.07, 95% CI [1.67-2.55]) to CLL. Among 1 487 patients receiving first-line treatment, 164 (11%) had T2D. Upon first-line treatment, patients with T2D had shorter event-free survival (HR 1.40, 95% CI [1.07-1.79]) and higher mortality (HR 1.22, 95% CI [0.95-1.56]) when compared with patients with CLL without T2D. Treatment with fludarabine, cyclophosphamide, and rituximab (FCR) was not associated with a superior survival compared with bendamustine and rituximab (BR) in patients with T2D (HR 2.58, 95% CI [0.61-10.86]). Summary/Conclusion: T2D is associated with an inferior prognosis in CLL. CLL patients with T2D had a lower probability of receiving CLL-treatment yet higher mortality. While the latter may be related to surveillance bias, further investigation in to causes is required. Though not statistically significant, analyses suggest that among patients with CLL and T2D, BCR treatment might be superior to FCR.